Ribavirin Inhibits the Activity of mTOR/eIF4E, ERK/Mnk1/eIF4E Signaling Pathway and Synergizes with Tyrosine Kinase Inhibitor Imatinib to Impair Bcr-Abl Mediated Proliferation and Apoptosis in Ph+ Leukemia

PloS One
Fangfang ShiTianyou Yan

Abstract

The eukaryotic translation initiation factor 4E (eIF4E), which is the main composition factor of eIF4F translation initiation complex, influences the growth of tumor through modulating cap-dependent protein translation. Previous studies reported that ribavirin could suppress eIF4E-controlled translation and reduce the synthesis of onco-proteins. Here, we investigated the anti-leukemic effects of ribavirin alone or in combination with tyrosine kinase inhibitor imatinib in Philadelphia chromosome positive (Ph+) leukemia cell lines SUP-B15 (Ph+ acute lymphoblastic leukemia cell line, Ph+ ALL) and K562 (chronic myelogenous leukemia cell line, CML). Our results showed that ribavirin had anti-proliferation effect; it down-regulated the phosphorylation levels of Akt, mTOR, 4EBP1, and eIF4E proteins in the mTOR/eIF4E signaling pathway, and MEK, ERK, Mnk1 and eIF4E proteins in ERK/Mnk1/eIF4E signaling pathway; reduced the expression of Mcl-1 (a translation substrates of eIF4F translation initiation complex) at protein synthesis level not mRNA transcriptional level; and induced cell apoptosis in both SUP-B15 and K562. 7-Methyl-guanosine cap affinity assay further demonstrated that ribavirin remarkably increased the eIF4E binding to 4EBP1...Continue Reading

References

Dec 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alex KentsisKatherine L B Borden
Oct 28, 2005·RNA·Alex KentsisKatherine L B Borden
Dec 14, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Masamitsu YanadaUNKNOWN Japan Adult Leukemia Study Group
Dec 7, 2007·Genes & Development·Hans-Guido WendelScott W Lowe
Feb 8, 2008·Cell Cycle·Ricardo L A Silva, Hans Guido Wendel
Apr 9, 2008·The Journal of Cell Biology·Biljana CuljkovicKatherine L B Borden
Aug 19, 2008·Biochemical and Biophysical Research Communications·Keith TanKatherine L B Borden
Nov 8, 2008·The Journal of Biological Chemistry·Yuxing ZhaoJeffrey C Rathmell
Jul 22, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christian GoetzMatthias Gromeier
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nissim Hay
Aug 13, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew C Hsieh, Davide Ruggero
Mar 19, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Filippa PetterssonWilson H Miller

❮ Previous
Next ❯

Citations

Jul 7, 2017·CA: a Cancer Journal for Clinicians·Harrys A TorresVincent Mallet
Nov 1, 2017·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J CaoD Chen
Jun 14, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Laura P M H de RooijKristin J Hope
Mar 5, 2020·Nucleosides, Nucleotides & Nucleic Acids·Alexander N PrutkovYulia V Berezovskaya
Mar 1, 2018·Oncotarget·Joshua CasaosNicolas Skuli
Nov 28, 2018·Oncogene·Karen A UrtishakCarolyn A Felix
Aug 3, 2017·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·S LiuM Lei
Sep 28, 2020·FEBS Open Bio·Vicente Morales-GarciaErick de la Cruz-Hernandez
Jul 3, 2019·Molecular Cancer Therapeutics·Joshua CasaosNicolas Skuli
Feb 12, 2019·Biochemical and Biophysical Research Communications·Jing JinAli Deng
Jun 15, 2020·Cellular Signalling·Xiaotong YangRuifeng Cao

❮ Previous
Next ❯

Methods Mentioned

BETA
density gradient centrifugation
PCR
pull-down
flow cytometry

Clinical Trials Mentioned

NCT00559091

Software Mentioned

SPSS17
QUANTITY ONE

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.